Inhibition of human α-methylacyl CoA racemase (AMACR): a target for prostate cancer

ChemMedChem. 2013 Oct;8(10):1643-7. doi: 10.1002/cmdc.201300179. Epub 2013 Aug 8.

Abstract

The enzyme α-methylacyl CoA racemase (AMACR) is involved in the metabolism of branched-chain fatty acids and has been identified as a promising therapeutic target for prostate cancer. By using the recently available human AMACR from HEK293 kidney cell cultures, we tested a series of new rationally designed inhibitors to determine the structural requirements in the acyl component. An N-methylthiocarbamate (Ki=98 nM), designed to mimic the proposed enzyme-bound enolate, was found to be the most potent AMACR inhibitor reported to date.

Keywords: AMACR; MCR; coenzyme A; inhibitors; α‐methylacyl CoA racemase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • HEK293 Cells
  • Humans
  • Male
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Protein Binding
  • Racemases and Epimerases / antagonists & inhibitors*
  • Racemases and Epimerases / genetics
  • Racemases and Epimerases / metabolism
  • Structure-Activity Relationship
  • Thiocarbamates / chemical synthesis
  • Thiocarbamates / chemistry
  • Thiocarbamates / metabolism

Substances

  • Enzyme Inhibitors
  • Thiocarbamates
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase